EPIDERMAL GROWTH-FACTOR BINDING IN THE DEVELOPING MALE REPRODUCTIVE DUCT AND ITS REGULATION BY TESTOSTERONE

It was Shown previously that epidermal growth factor (EGF) plays a rol e in the testosterone-dependent fetal Wolffian duct differentiation. I n this communication, the role of EGF was further investigated by dete rmining whether EGF receptor plays a role in mediating the effect of E GF during Wolffian duct (male duct) differentiation, and experiments w ere designed to test this hypothesis. EGF-binding activity in cultured cells isolated from the reproductive ducts of 14- to 18-day-old fetal mouse was determined, and the results were evaluated by saturation/Sc atchard analysis. Using this analysis, we demonstrate that the fetal m ouse Wolffian duct contains EGF-saturable EGF-binding proteins with a binding affinity of 10(-10) m. The binding was temperature, time, and cell concentration dependent. Affinity cross-linking analysis of EGF b inding of this tissue indicated the presence of an EGF receptor protei n of 150 kilodaltons mol wt. The binding activity increased in paralle l with the progression of Wolffian duct differentiation during the 14t h to 18th day of gestation, which is the critical period of Wolffian d uct differentiation. The binding activity was barely detectable at the onset of differentiation, i.e. on the 14th day of gestation. Binding activity in the male duct was higher than that in the female duct. Pre natal administration of testosterone during days 13-17 of gestation in creased the EGF receptor concentration in the masculinized female fetu ses, suggesting a role of fetal testicular testosterone in determining EGF-binding activity. Prenatal treatment of cyproterone acetate (an a ntiandrogen at the level of androgen receptor binding to androgen), ho wever, produced no effect on EGF-binding activity in male fetuses. Thu s, a role for the EGF receptor is indicated during Wolffian duct diffe rentiation. Testosterone appears to play a role in modulating EGF-bind ing activity. Further work is necessary to determine the mechanism by which testosterone modulates EGF-binding activity in this tissue.